There is no legal obligation for health services research by AMNOG. Nevertheless, health services research is becoming increasingly important even in times of AMNOG. This becomes particularly clear in view of the discussion about benefit assessments in the area of the so-called existing market. The term existing market describes active ingredients that were approved before 2011 and still enjoy documentation protection. This article uses the individual legal regulations of AMNOG to show possible starting points for health services research.

The federal government has recognized the importance of health services research for health care in the last three years and has brought the still more scientific research discipline of health services research into the health policy discussion: In the coalition agreement between the CDU, CSU and FDP in October 2009, there was a separate section on the topic Health services research, which ends with the statement, “we [will] systematically expand health services research.” In March 2010, the then Federal Minister of Health Dr. Philipp Rösler said this in the cover interview with “Monitor Healthcare Research” (2/2010) with the statement: “Healthcare research is a very important topic for me. This is precisely why the term […] appears twice in the coalition agreement – once in the BMBF and once in the BMG part.”

The Pharmaceutical Market Reorganization Act
(AMNOG) has been in force since January 1, 2011. Since then, pharmaceutical companies have been obliged to demonstrate the additional benefit of their medicines compared to the appropriate comparative therapy when they launch new products on the market. For this purpose, a so-called benefit dossier must be submitted (Section 35a SGB V). Only if there is proof of an additional benefit recognized by the Federal Joint Committee (G-BA) will agreement discussions regarding a reimbursement amount be held between the National Association of Statutory Health Insurance Funds and the pharmaceutical company (Section 130b SGB V). If no agreement is reached, an arbitration award will be required and a reimbursement amount will be determined based on European comparative prices. For medicines without proven additional benefit, the medicine is added to a fixed amount group or the reimbursement amount is limited to the price of comparable medication. Deviating from or supplementing the procedure outlined, contracts (according to Section 130c SGB V) between health insurance companies and pharmaceutical manufacturers are possible. Cost-benefit assessments by the IQWiG (according to Section 35b SGB V) also have the character of an optional and downstream “can” clause in this newly established procedural route.
The focus when implementing the new legal regulations is currently still on the new active ingredients that were or will be brought onto the market after January 1, 2011. The potential support provided by health services research is often not considered. Ultimately, there is no health care research data before market entry - with the possible exception of international data, where there is the problem of limited transferability of the results to the German health care reality. Nevertheless, there are numerous interfaces and starting points for the use of health services research in the context of AMNOG, which are presented below.
Starting points: comparative therapy and existing market
While there are no health services research findings available for new drugs, there are such data as well as health care research studies on so-called “appropriate comparative therapies”. In addition, the topic of benefit assessment will probably also become relevant for the existing market this year. This addresses active ingredients that were already on the market before 2011 and still enjoy document protection. Data from everyday care is already available on these active ingredients.
Against this background, the question arises as to where there are starting points for the use of health services research. This will be worked out below using the four paragraphs 35a, 130b, 130c and 35b SGB V, which are the focus of the newly regulated price setting.

§ 35a: Benefits dossier
In the benefit dossier, statements must be made in particular on the following points (cf. § 35a SGB V: Assessment of the benefits of drugs with new active ingredients):
1. Approved areas of application
2. Medical benefits
3. Additional medical benefit in relation to the appropriate comparator therapy
4. Number of patients for whom there is a therapeutically significant additional benefit
5. Costs of therapy for statutory health insurance
6. Requirement for a quality assured application
Since health care data is already available for the appropriate comparative therapy, this is a suitable starting point for using routine data. On the one hand, a prescription data-based weakness analysis of the comparison therapy (point 3) can be carried out. This makes sense insofar as the new drug (probably) does not have these weaknesses. On the other hand, the prescription data for the comparative therapy can be used to better estimate the number of patients and the annual therapy costs (points 4+5). When looking at the existing market, the “real data” perspective can also be taken for the active ingredient itself being evaluated.
Starting points for such secondary data-based analysis approaches can, for example, B. be:
• Patient profiles for indications in which patient groups the highest additional benefit can be expected
• Compliance or Duration of adherence to therapy for initial indications of the tolerability of the therapy
• Comedications for an insight into the increased occurrence of other clinical pictures
• Therapy costs for comparing the costs of main and secondary medications for different therapeutic approaches*

The demand to make greater use of health services research in cost-benefit assessments was made in 2007, long before the first AMNOG drafts. This was done e.g. B. in the “10 Hanover Theses on the Contribution of Health Services Research to the Cost-Benefit Assessment of Drugs” from June 5, 2007, which several scientists - including Prof. Neubauer (Institute for Health Economics Munich), Prof. Schwartz (Hannover Medical School), Prof. Scriba (LMU Munich) and Prof. Augustin (University Hospital Hamburg-Eppendorf) - have drawn up together.

§ 130b: Price negotiations
As part of the price negotiations according to Section 130b, i.e. the “agreements between the umbrella association of the Federation of Health Insurance Funds and the pharmaceutical companies on reimbursement amounts for medicines”, different aspects will play a role:
• the result of the benefit assessment or the extent of the additional benefit (significant, considerable, small)
• the annual therapy costs of the appropriate comparative therapy or, in the case of different indications, the appropriate comparative therapies
• the current product price, which can still be freely determined by the entrepreneur upon approval
• Information on the entire therapy
costs of the different therapeutic approaches, for example the costs of the expected accompanying therapies, therapies against side effects, possible conversion therapies, hospital admissions, etc.
The real therapy costs form a starting point for health services research. Such therapy cost comparisons can be created on the basis of health care research studies. While this information may only be collected to a very limited extent for the new active ingredient, such studies are feasible for the comparative therapies. Such studies also provide indications of the costs of the new therapeutic approach, which can be expected based on the assessed additional benefit. When evaluating active ingredients from the existing market, this information can be collected in advance for both/all therapeutic approaches.
Health care research studies can therefore be used for argumentation in price negotiations (reimbursement amount agreements) – both by the pharmaceutical company and by the leading association. The experiences from the first agreement discussions now underway will show to what extent only information that has already been mentioned in the dossiers is used, or whether further information is accepted for argumentation.

§ 130c: Supplementary/replacing value-added contracts
The practical relevance of paragraph § 130c on contracts between health insurance companies and pharmaceutical companies is still questionable, as the previous agreements on the reimbursement amount are likely to significantly reduce the negotiation potential. Nevertheless, this set of instruments offers an interesting approach, especially when new findings emerge within healthcare under everyday conditions, in which healthcare research can play a role from several aspects:
• when selecting suitable contractual partners
• to support arguments in contract negotiations
• for scientific support of the contracts
Not every indication has the same importance for every health insurance company. This means that when selecting a potential contractual partner, a pharmaceutical manufacturer can take into account the respective potential of the indication based on routine data. In addition, evaluations of the real data can support both sides of the contract in the negotiations. Finally, when concluding a value-added contract, scientific support should also be agreed - not least for the purpose of fair pricing.

§ 35b: Cost-benefit assessment
The possible support services of benefit assessments through health services research have already been addressed under Section 35a SGB V (“Benefit dossiers”). After an arbitration award, both the federal association and the manufacturer can apply to the G-BA for a cost-benefit assessment. This can be done according to Section 35b SGB V, taking health care studies into account. However, it is not yet clear what is meant by health care studies.
Even one year after the start of AMNOG, no rules of procedure are in force. The design of such studies therefore remains questionable. The German Network for Healthcare Research criticizes the missing word “research” (see title interview with Prof. Pfaff and Prof. Harder in MVF 06/2011: “Discourse around the important word research”). In a statement on the health policy discussion about the allocation of scarce resources, Pfaff et al. write: “In view of the complexity of health services research and the long path involved in establishing health services research in Germany, one should speak of health services research studies here. This is not intended as a semantic gimmick, but is intended to emphasize the serious nature and high methodological standards that underlie this approach.” (Pfaff et al.: Health services research: indispensable in allocation decisions – a statement). The German Ethics Council also pointed out in a statement that the actual benefits of a drug often only become apparent years after approval and, among other things, should be checked and proven with the help of health services research studies.

Conclusion
As it turns out, health services research opens up some opportunities in the context of AMNOG, even if the benefits of health services research for everyone involved, such as industry, health insurance companies and, last but not least, patients, are by no means guaranteed. Depending on the paragraph under consideration, there are different starting points for the sensible use of health services research. One thing is certain: those who only work strictly according to the “AMNOG specifications” will miss the opportunities that arise and let others pass them by. <<

by: Dr. Andre Kleinfeld
Christian Bensing*